Nonmedical prescription drug misuse (NPDM) involving scheduled (controlled) medications (i.e., opioid analgesics, stimulants, tranquilizers) has significantly increased over the past two decades in the United States and is most prevalent among individuals 18 years of age. While there have been advances in understanding NPDM, considerable gaps in knowledge remain due to limitations in measurement and study designs and no national studies have examined longitudinal trajectories of NPDM among adolescents and most existing studies fail to account for important characteristics of NPDM such as motives, route of administration, and co- ingestion with other drugs. Findings from our two small exploratory cross-sectional projects (R03DA018239 and R03DA0187272) indicate that there are at least two behavioral subtypes of NPDM (self-treatment and recreational) subsumed under current measures used to assess NPDM, and these behavioral subtypes appear to differ in terms of adverse consequences. However, there is little published information regarding the long- term patterns of misuse and adverse outcomes associated with NPDM among adolescents in the United States. Existing cross-sectional and longitudinal panel data from the Monitoring the Future (MTF) study provide an unprecedented opportunity to address research questions that will lead to a more comprehensive understanding of NPDM and its consequences among adolescents. The objective of the proposed study is to advance our knowledge regarding longitudinal trajectories of NPDM using twelve independent, nationally representative cohorts of approximately 180,000 high school seniors between 1997 and 2008 from the MTF study. The MTF panel sample features twelve separate cohorts of approximately 28,800 high school seniors (modal age 18) who were followed 1-2 years (modal ages 19-20) and 3-4 years (modal ages 21-22) later, resulting in three waves of data. The proposed study aims to 1) assess NPDM and characteristics of NPDM (e.g., motives, route of administration, co-ingestion with other drugs) associated with three prescription drug classes (opioid analgesics, stimulants, tranquilizers), and determine the associations among NPDM, characteristics of NPDM, psychosocial risk factors, and adverse outcomes (e.g., health, legal and social) using cross-sectional and panel data; 2) identify longitudinal trajectories of NPDM of three prescription drug classes (opioid analgesics, stimulants, tranquilizers) across the developmental transition of greatest risk for NPDM- related adverse outcomes using panel data (i.e., ages 18-22), and examine variations in these trajectories by demographic factors, psychosocial risk and protective factors, and NPDM characteristics; and 3) examine the associations among longitudinal trajectories of NPDM of three prescription drug classes (opioid analgesics, stimulants, tranquilizers), important developmental transitions (e.g., college attendance, employment) and adverse outcomes (e.g., health, legal and social) during emerging adulthood using panel data. Findings from this project will substantially advance the current understanding of NPDM among adolescents in the United States, and provide information that will improve the screening, assessment, prevention, and treatment of prescription drug abuse.